Many plant polysaccharides exhibit apparent biological activities and are widely used for medicinal purposes [Bhushan Patwardhan and Manish Gautam. Botanical immunodrugs: scope and opportunities. //Reviews. DRUG DISCOVERY TODAY. 2005. Vol. 10. P. 495-502]. Compared to bacterial and synthetic analogues, botanical polysaccharides have no side effects and are of low toxicity, which give them considerable advantages during the development of immunomodulatory, antitumor, and wound healing substances [Schepetkin L. A., Quinn M. T. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential. //Int. Immunopharmacol. 2006. Vol. 6. P. 317-333].
The role of dendritic cells in the immune response was first studied by Ralph Steinman [Jacques Banchereau & Ralph M. Steinman. Dendritic cells and the control of immunity. //Nature, 19 Mar. 1998, Vol. 392: 245-52]. Dendritic cells play a key role in the control of the immune response; they capture foreign antigens and stimulate T cell responses. The vaccination outcome and immune response to infection depend on dendritic cells [Howard C J, Charleston B, Stephens S A, Sopp P, Hope J C. The role of dendritic cells in shaping the immune response. //Anim Health Res Rev, 2004, 5(2):191-5]. Therefore, dendritic cells attract close attention as a target for immunomodulatory agents [Mohty M., Gaugler B, Mami N B, Olive D. Regulation of Dendritic Cell Function with Immunomodulatory Drugs Current Medicinal Chemistry. //Anti-Inflammatory & Anti-Allergy Agents, 2005, Vol. 4, No. 2, pp. 169-175(7)].
There is a known method of producing plant-derived polysaccharides with immunomodulatory activity, which involves treating a plant raw material with a formalin water solution, keeping it in acidified water, and then extracting pectic polysaccharides with an ammonium oxalate water solution, treating the extract in a known way, and freeze-drying the desired product. Freshwater flowering plants, e.g., any type of duckweed (Lemna spp.) or previously chopped, fresh aerial parts of higher plants, e.g., bladder campion (Oberna behen (L)) are used as plant raw materials (Russian Patent 2149642 C1, A 61 35/78, 27.05.2000). However, the produced pectic substances have very low immunostimulatory activity (the stimulation index for neutrophils and macrophages is 1.09 to 1.12 and 1.12 to 1.39, respectively) and do not have activity towards dendritic cells.
There is a known substance with anti-infective activity and without hemagglutinating activity, which is obtained from dividing cells of plants (corn, potato, mushroom) and is named as Gamma-plant (γ-PL) (L. A. Chekanovskaya, Russian Patent 2028303 C1, C08B37/00). Physical-chemical properties of the biologically active substance Gamma-plant have been described. The latter is a glycoprotein with a molecular weight of 900-2000 kD, consisting of carbohydrate and protein portions with the percent weight ratio of 90:10. At the same time, the carbohydrate portion of the substance comprises 70-80% of glucose and 12-18% of uronic acid.
Disadvantages of the known solution are the mitogenic activity of the substance, which may lead to polyclonal activation of cells, making it dangerous to use the substance as a drug, and the absence of immunostimulatory activity towards dendritic cells and macrophages.
There is also a known method of producing a substance with immunostimulatory, antiviral, and antimicrobial activities, the substance produced using the said method, and a pharmaceutical composition based on the said substance (Russian Patent no. 2195308 A 61K 35/78, 27.12.2002). This method involves extracting the chopped plant raw material with water, centrifuging, concentrating, and precipitating the aqueous extract, and purifying and drying the desired product. Plants of Dioscoreaceae, Plantaginaceae, and Solanaceae families can be used as plant raw materials. Precipitation is performed with 96% ethanol in the presence of sodium chloride. The precipitate is re-precipitated with a salt or acidic agent, and the raw acidic peptidoglycan thus obtained is treated with alkali or a saturated solution of alkali metal salt. The desired product is purified using gel permeation chromatography. The substance produced using this method is a water-soluble acidic peptidoglycan having a molecular weight of 1200-40000 kD and glucose to uronic acid weight ratio of 1 to 2-4. The peptide portion of the molecule of acidic peptidoglycan is 13±3 wt %.
The disadvantage of the known method concerns the difficulty of precipitation (consequent reprecipitation with ethanol). The known substance does not have immunostimulatory activity towards dendritic cells.